Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma.
Integrin-linked kinase, phosphorylated AKT and the prognosis of malignant pleural mesothelioma.
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DOI：
10.1016/j.ejcts.2010.05.007
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
S. Watzka;U. Setinek;E. Stubenberger;M. Tötsch;G. Dekan;M. Marcher;T. Fleck;Michael R. Müller
中科院分区：
文献类型：
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作者：
S. Watzka;U. Setinek;E. Stubenberger;M. Tötsch;G. Dekan;M. Marcher;T. Fleck;Michael R. Müller
目的：整合素连接激酶（ILK）是一种细胞膜结合分子，参与多种肿瘤的转移进程。它磷酸化下游靶AKT（磷酸化AKT，pAKT），并通过这样做，它激活抗凋亡途径。我们最近发现ILK在恶性胸膜间皮瘤（MPM）中表达。为了确定是否ILK表达MPM与pAKT表达，以及ILK和pAKT表达是否对患者的预后有任何影响，我们相关的ILK和pAKT表达，通过免疫组化评估，与疾病相关的生存在一个回顾性队列的80 MPM patients.Material和方法：石蜡标本的80 MPM病例治疗从1990年至2006年（52例手术病例，28例保守病例）已检索档案。患者的中位（范围）年龄为62岁（28-83岁）;男女比例为3：1。50%的患者具有上皮样亚型。样品用抗ILK和抗pAKT染色，并由两名独立的病理学家评分。ILK和pAKT的表达强度与疾病相关的survival.Results：总共，73 80（91%）MPM样品表达ILK，65 74（88%）MPM样品表达pAKT。根据ILK或pAKT表达比较5年疾病相关生存率，在ILK和pAKT表达或不表达患者之间未发现统计学显著差异。然而，在保守治疗的MPM患者亚组中，ILK强表达的患者的5年疾病相关生存期较长（p <0.0001）。总的来说，所有ILK、pAKT和治疗亚组中唯一的预后因素是组织学亚型（p= 0.01）。结论：ILK在MPM中的表达与下游靶基因pAKT的表达有关，但ILK和pAKT的表达对MPM患者的预后无明显影响，但对某些MPM亚群的预后影响除外。然而，为了阐明ILK和pAKT表达在MPM中的真实预后影响，需要进行前瞻性试验。
Objective:Integrin-linked kinase (ILK) is a cell membrane-bound molecule implicated in the metastatic progression of many tumour types. It phosphorylates the downstream target AKT (phosphorylated AKT, pAKT), and, by doing this, it activates anti-apoptotic pathways. We have recently shown ILK expression in malignant pleural mesothelioma (MPM). To determine whether ILK expression in MPM is connected with pAKT expression, and whether ILK and pAKT expression have any influence on the patient’s prognosis, we correlated ILK and pAKT expression, as assessed by immunohistochemistry, with disease-related survival in a retrospective cohort of 80 MPM patients.Material and methods:The paraffin specimens of 80 MPM cases treated from 1990 to 2006 (52 surgical cases, 28 conservative cases) have been retrieved from the archive. The median (range) patients’ age was 62 (28–83 years) years; the male-to-female ratio was 3:1. Fifty percent of the patients had an epitheloid subtype. The samples have been stained with anti-ILK as well as with anti-pAKT and scored by two independent pathologists. Intensity of ILK and pAKT expression has been correlated with disease-related survival.Results:In total, 73 of 80 (91%) MPM samples expressed ILK; 65 of 74 (88%) MPM samples expressed pAKT. Comparing the 5-year disease-related survival according to ILK or pAKT expression, no statistically significant difference could be found between ILK and pAKT expressing or non-expressing patients. However, in the subgroup of conservatively treated MPM patients, those with strong ILK expression had a longer 5-year disease-related survival (p≪ 0.0001). In total, the only prognostic factor across all ILK, pAKT and therapy subgroups was the histological subtype (p= 0.01). The prognostic significance of the histological subtype has been confirmed in multivariate analysis (p= 0.005).Conclusion:The expression of ILK in MPM is connected with the expression of the downstream target pAKT, but neither ILK nor pAKT expression has a measurable influence on the patient’s prognosis, except for certain subgroups of MPM. However, to shed light on the true prognostic impact of ILK and pAKT expression in MPM, prospective trials are needed.